As opposed to IgE mediated food allergy (IFA) which can cause fatal outcomes, non-IgE mediated FA (NFA) was initially thought to be a benign condition mediated by cellular immune responses, primarily affects the GI mucosa. NFA children were thought to recover well upon avoidance of offending food. Although pathogenesis of NFA is still not well understood, recent studies indicate widely variable clinical manifestations of NFA. In parallel to our better appreciation of clinical features of NFA, complex regulatory mechanisms of gut immune homeostasis have become known with progress in our understanding of the gut mucosal immune system. In addition, a role of gut commensal flora on the gut immune system has also become better understood along with the effects of dietary components. Subtle changes in interactions between environmental factors (microbiota, dietary components, etc) and the gut immune responses can affect gut immune homeostasis, which can result in undesired adverse reactions to food proteins (FPs). This review discusses recent progress in our understanding of the regulatory mechanisms of gut immune homeostasis and recently revealed widely variable clinical presentations of NFA with respect to it pathogenesis.

Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey- New Jersey Medical School, Newark, NJ, United States. jyanouha@umdnj.edu.